Chemical compounds in coffee — especially phenylindanes that form during the roasting of coffee beans — appear to prevent the damaging aggregation of amyloid-beta and tau known to play key roles in Parkinson’s and Alzheimer’s disease, researchers report.
Caffeine, in contrast, had no effect on protein buildup in this early lab study, and researchers saw coffee consumption to offer no protection against alpha-synuclein aggregation.
Coffee consumption has been suggested to reduce the risk of developing diabetes, various cancers, and neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Despite the available evidence, however, it’s unclear what how exactly coffee can help to prevent age-related cognitive decline.
Past studies have reported that caffeine, the main bioactive compound of coffee, can reduce the risk of Parkinson’s both in men and in women who were not taking hormone replacement therapy. It has also been seen to reduce nerve cell death in the substantia nigra – the brain area most affected in Parkinson’s – in mouse models of the disease.
However, recent data also suggests that long-term consumption of caffeine may exacerbate anxiety-related behavioral and psychological symptoms in patients with dementia, counteracting its potential beneficial effects.
These contrasting findings highlight the need to identify those coffee components that may be neuroprotective.
Researchers led by Donald Weaver, MD, PhD, co-director of the Krembil Brain Institute, evaluated the potential of chemical components of coffee to inhibit the buildup of proteins that can drive neurodegenerative diseases like Alzheimer’s and Parkinson’s, in particular: amyloid-beta, tau, and alpha-synuclein.
The team started by examining three types of instant coffees — light roast, dark roast, and decaffeinated dark roast — in terms of their ability to prevent protein aggregates. They tested the instant coffees by adding them to one of these three proteins in an in vitro (laboratory dish) context.
“The effect of caffeine content would be assessed by comparing the activity of caffeinated and decaffeinated dark roast coffee extracts. Further, since it is known that different levels of roasting affect the composition of the coffee brew, comparison of light versus dark roast coffee extracts was also performed,” the researchers wrote.
Dark roast coffee showed the greatest inhibitory effect against tau protein buildup. Interestingly, the level of caffeine in each type of coffee had no impact on tau, amyloid-beta, and alpha-synuclein’s ability to aggregate.
“We were surprised to find that caffeine content did not influence aggregation inhibition, and thus performed a post-hoc analysis of pure caffeine,” the researchers said in the study. “No effect on fibril growth was observed relative to the vehicle control, consistent with the results for caffeinated versus decaffeinated coffee extracts.”
Further experiments found that all coffee extracts could prevent amyloid-beta and tau protein aggregation at 200 ?g/mL concentration. Dark roast coffee (with or without caffeine) was seen as more potent in preventing the oligomerization — a chemical form that proteins can take — of amyloid-beta than the light roast extract.
All types of coffee as an instant mix, however, showed an ability to promote alpha-synuclein aggregation at amounts above 100 mg/mL.
To better understand these findings, the team then explored the activity of the six main chemical components of coffee — caffeine, chlorogenic acid, quinic acid, caffeic acid, quercetin, and phenylindane.
Researchers found that most of these compounds — with exception of caffeine and quinic acid for amyloid-beta, and caffeine and caffeic acid for tau — prevented protein aggregation.
Phenylindane was found to hold the strongest inhibitory activity, working as a dual-inhibitor to prevent the formation of amyloid-beta aggregates by 99% and those of tau tangles by 95.2%. Importantly, in later experiments, phenylindanes did not show “pro-aggregation behavior” toward alpha-synuclein, the study reported.
Phenylindanes are formed during the roasting of coffee beans and are found in higher concentrations in dark roast coffees, which have longer roasting times.
“It’s the first time anybody’s investigated how phenylindanes interact with the proteins that are responsible for Alzheimer’s and Parkinson’s,” Ross Mancini, a research fellow in medicinal chemistry at the Krembil institute and the study’s first author, said in a news release. “The next step would be to investigate how beneficial these compounds are, and whether they have the ability to enter the bloodstream, or cross the blood-brain barrier.”
The team is now investigating if phenylindanes can reduce amyloid-beta, tau and alpha-synuclein loads in cell and animal models of Alzheimer’s and Parkinson’s disease.
Researchers caution that their findings are not recommendation for excessive coffee consumption.
“What this study does is take the epidemiological evidence and try to refine it and to demonstrate that there are indeed components within coffee that are beneficial to warding off cognitive decline,” Weaver said. “It’s interesting, but are we suggesting that coffee is a cure? Absolutely not.”